1,3-Benzodithiolanes

ABSTRACT

Compounds having the formula ##STR1## and the pharmaceutically acceptable salts thereof, wherein R 1  is hydrogen, halogen, trifluoromethyl, alkyl, alkoxy, nitro, amino, or hydroxy; R 2  is carboxyl or alkoxycarbonyl; and n is 0, 1, 2, 3, 4 or 5; have antiinflammatory activity.

This is a division, of application Ser. No. 705,849, filed July 16,1976.

SUMMARY OF THE INVENTION

1,3-Benzodirthiolanes having the formula ##STR2## and thepharmaceutically acceptable salts thereof, have antiinflammatoryactivity. In formula I, and throughout the specification, the symbolsare as defined below.

R₁ can be hydrogen, halogen, trifluoromethyl, alkyl, alkoxy, nitro,amino or hydroxy;

R₂ can be:

I. A GROUP HAVING THE FORMULA ##STR3## wherein R₃ and R₄ are the same ordifferent and are hydrogen, alkyl or hydroxyalkyl;

II. A GROUP HAVING THE FORMULA ##STR4## WHEREIN M IS 0 OR 1, A isoxygen, sulfur, CH--R₅ or N--R₆, R₅ is hydrogen or alkyl and R₆ ishydrogen, alkyl, monohydroxyalkyl or phenyl, provided that when m is 0,A is CH--R₅ ;

iii. a group having the formula ##STR5## wherein R₇ and R₈ are eachhydrogen or together R₇ and R₈ are ═CH--(CH₂)_(p) --R₉ wherein p is 0 oran integer from 1 to 9 and R₉ is hydrogen, carboxy, alkoxycarbonyl,alkyl, phenyl or phenyl mono- or disubstituted with trifluoromethyl,halogen (preferably fluorine), or alkoxy;

IV. A GROUP HAVING THE FORMULA ##STR6## wherein R₁₀ is hydrogen,phenylalkyl, halophenylalkyl, benzoyl or halobenzoyl, and R₁₁ ishydrogen, halogen or alkoxy; or

V. A GROUP HAVING THE FORMULA ##STR7## wherein R₁₂ can be hydrogen oralkyl; and

N IS 0, 1, 2, 3, 4 OR 5.

The terms "alkyl" and "alkoxy," as used throughout the specification,whether alone, or as part of a larger group, refer to groups having 1 to4 carbon atoms.

The term "halogen" (or "halo"), as used throughout the specification,whether alone, or as part of a larger group, refers to fluorine,chlorine, bromine and iodine.

Exemplary of the heterocyclic moieties contemplated by the formula##STR8## are 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl,4-thiamorpholinyl, 1-piperazinyl, 4-alkyl-1-piperazinyl,4-alkyl-1-piperidinyl, 3-alkyl-1-pyrrolidinyl,4-hydroxyalkyl-1-piperazinyl and 4-phenyl-1-piperazinyl.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of this invention can be prepared using as startingmaterials 1,2,3-benzothiadiazoles having the formula ##STR9## andarylisothiocyanates having the formula

    III aryl--N═C═S.

the 1,2,3-benzothiadiazoles of formula II are readily obtainable using,for example, the procedure described by Jacobsen, Ann., 277: 209-261(1893). Arylisothiocyanates of formula III are well known compounds andare readily obtainable using art recognized procedures; see, forexample, Hodgekins, J. Org. Chem., 29: 3098 (1964).

Reaction od a 1,2,3-benzothiadiazole of formula II with anarylisothiocyanate of formula III yields an intermediate having theformula ##STR10##

The reaction is run at an elevated temperature (preferably above about200° C), and preferably in an inert atmosphere such as argon ornitrogen; see Huisgen, Experentia, 17, 566 (1961).

The precursor of a compound of formula I is a quaternary salt of a1,3-benzodithiolane of formula IV. Quaternization of a compound offormula IV can be accomplished by reacting the compound with analkylating agent. The particular alkylating agent used is not critical.However, the most readily available (and, therefore, preferred)alkylating agents are those having the formula

    V R.sub.13 --X,

wherein R₁₃ is a substituted or unsubstituted phenyl group, or an alkylgroup, and X is a sulfonyl group or halogen group. Exemplary alkylatingagents are methanesulfonate, benzenesulfonate, p-toluenesulfonate,methyl iodide, methyl bromide, methyl fluoride and methyl chloride.

Reaction of a quaternary derivative of a compound of formula IV with aprimary amine having the formula

    V NH.sub.2 --(CH.sub.2).sub.n --R.sub.2

yields a product of formula I. The reaction is preferably run in a polarorganic solvent, e.g., dimethylformamide or dimethylsulfoxide, in thepresence of a base, e.g., an alkali metal carbonate such as sodiumcarbonate.

The acid addition salts of the compounds of formula I can be preparedusing procedures well known in the art. Exemplary organic and inorganicacids are the hydrohalides, especially the hydrochloride andhydrobromide, sulfate, nitrate, phosphate, borate, acetate, tartrate,maleate, citrate, succinate, benzoate, ascorbate, salicylate,methanesulfonate, benzenesulfonate, benzenesulfonate and the like.

Many alternative procedures for the preparation of the compounds of thisinvention will be apparent to the practitioner of this invention. Forexample, the compounds of formula I wherein R₂ is carboxyl can beprepared by saponification of a corresponding compound wherein R₂ isalkoxycarbonyl. An alternative method for preparing the compounds offormula I wherein R₂ is an N-substituted indole comprises first formingthe corresponding indole compound wherein the nitrogen atom isunsubstituted and then using conventional procedures to add thesubstituent.

The compound of formula I having the formula ##STR11## are preferablyprepared by reacting an aldehyde having the formula ##STR12## with acorresponding 1,3-benzodithiolane having the formula ##STR13##

The compounds of formula I and the pharmaceutically acceptable saltsthereof can be used in the treatment of inflammation in mammalianspecies such as rats, dogs, cats, monkeys, etc. Joint tenderness andstiffness (in conditions such as rheumatoid arthritis) can be treatedwith the abovedescribed compounds. The compounds of this invention canbe formulated for use as antiinflammatory agents according to acceptablepharmaceutical practice in oral dosage forms such as tablets, capsules,elixirs or powders or in an injectable form in a sterile vehicleprepared according to conventional pharmaceutical practice. Thecompounds of this invention can be administered in amounts of 100milligrams per 70 kilograms of animal body weight per day to 2 grams per70 kilograms of animal body weight per day, preferably 100 milligramsper 70 kilograms of animal body weight per day to 1 gram per 70kilograms of animal body weight per day.

The following preparations are included to further describe thepreparation of compounds which are useful intermediates in thisinvention.

PREPARATION 1 5-Chloro-N-methyl-N-phenyl-1,3-benzodithiol-2-iminiumiodide

A. 5-chloro-N-phenyl-1,3-benzodithiol-2-imine

Phenylisothiocyanate (8.8g) and 5-chloro-1,2,3-benzothiadiazole (3.75g)are combined under an inert atmosphere and heated at 220° C untilnitrogen evolution ceases. Initial purification of the product isaccomplished by dry column chromatography (600g alumina column, benzenesolvent). The product is further purified with a methylene chloride washand recrystallization (twice) from pentane to yield 1.5g of the titlecompound, melting point 71°-73° C.

B. 5-chloro-N-methyl-N-phenyl-1,3-benzodithiol-2-iminium iodide

A solution of 5-chloro-N-phenyl-1,3-benzodithiol-2-imine (6.0g) andmethyl iodide (50 ml, excess) in 200 ml of dry benzene is heated at 50°C for 72 hours. The reaction mixture is filtered and the resultant solidis washed several times with pentane. The solid product isrecrystallized from n-amyl alcohol to yield 4.0g of the title compound,melting point 205°-207° C.

Anal. Calc'd. for C₁₄ H₁₁ ClNS₂ ·I: C, 40.06; H, 2.64; N, 3.34; Cl,8.45; I, 30.24; S, 15.28. Found: C, 40.26; H, 2.84; N, 3.31; Cl, 8.31;I, 29.98; S, 15.07.

PREPARATION 25-Chloro-1,3-benzodithiol-2-ylidene-4-fluoro-N-methylbenzaminium iodide

A. n-(5-chloro-1,3-benzodithiol-2-ylidene)-4-fluorobenzenamine

p-Fluorophenylisothiocyanate (25g) and 5-chloro-1,2,3-benzothiadiazole(8.5g) are combined under an inert atmosphere and heated at 220° C untilthe evolution of nitrogen ceases. Excess p-fluorophenylisothiocyanate isremoved in vacuo. The residue is initially purified by columnchromatography (600 ml activity III alumina, cyclohexane solvent). Thesecond fraction obtained is divided into two equal portions and purifiedby dry column chromatography (alumina, benzene/cyclohexane solvent)yielding 3.5g of material. This material is recrystallized three timesfrom pentane to yield 2.8g of the title compound, melting point101°-102° C.

B. 5-chloro-1,3-benzodithiol-2-ylidene-4-fluoro-N-methyl-benzaminiumiodide

A solution of N-(5-chloro-1,3-benzodithiol-2-ylidene-4-fluorobenzenamine(1.4g) and methyl iodide (10 ml) in benzene (20 ml) is heated at refluxfor three weeks. The resultant precipitate is collected by filtrationand recrystallized from acetonitrile/benzene to yield 1.9g of the titlecompound, melting point 205°-206° C.

Anal. Calc'd. for C₁₄ H₁₀ ClFINS₂ : C, 38.42; H, 2.30; N, 3.19; S,14.65; Cl, 8.10; I, 29.01. Found: C, 38.41; H, 2.26; N, 3.15; S, 14.94;Cl, 7.93; I, 29.18.

PREPARATION 3 N-(1,3-Benzodithiol-2-ylidene)-N-methylbenzaminium iodide

A. 2-(phenylimino)-1,3-benzodithiole

Phenylisothiocyanate (12.15g) and 1,2,3-benzothiodiazole (4.08g) arecombined and heated at 200°-220° C under an inert atmosphere untilnitrogen evolution ceases. The reaction mixture is initially purified bycolumn chromatography (500 ml activity I alumina, cyclohexane solvent)to yield 2.8g of crude 2-(phenylimino)-1,3-benzodithiole. The crudesolid is further purified by column chromatography (30 ml activity Ialumina, pentane solvent) to yield 1.9g of the title compound, meltingpoint 67°-68° C.

B. n-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide

A solution containing 2-(phenylimino)-1,3-benzodithiole (2.3g) in 50 mlof methyl iodide is heated at reflux for twenty-four hours. Theprecipitate obtained is filtered and washed several tims with benzene.The yellow solid is recrystallized from acetonitrile to yield 2.0g ofthe title compound, melting point 220°-230° C (dec.).

Anal. Calc'd. for C₁₄ H₁₂ NS₂.I: C, 43.64; H, 3.14; N, 3.64; S, 16.65;I, 32.94. Found: C, 43.69; H, 3.25; N, 3.57; S, 16.65; I, 32.68.

PREPARATION 4N-(5-Methoxy-1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide

A. n-(5-methoxy-1,3-benzodithiol-2-ylidene)benzenamine

A solution of 5-methoxy-1,2,3-benzothiadiazole (5 g) in 50 ml of phenylisothiocyanate is heated at 220° C under an inert atmosphere until theevolution of nitrogen ceases (about two hours). The excess phenylisothiocyanate is removed in vacuo. The resultant residue ischromatographed on silica gel (500 ml) eluting withpentane/dichloromethane (4:1). Fractions containing the desired product(R_(f) =0.2, silica gel, benzene) are combined and concentrated invacuo. The resultant solid is recrystallized from pentane to yield 2.8 gof the title compound, melting point 58°-60° C.

Anal. Calc'd. for C₁₄ H₁₁ NOS₂ : C, 61.51; H, 4.06; N, 5.12; S, 23.46.Found: C, 61.46; H, 3.97; N, 5.21; S, 23.68.

B. n-(5-methoxy-1,3-benzodithiol-2-ylidene)-N-methylbenzenaminium iodide

A solution of N-(5-methoxy-1,3-benzodithiol-2-ylidene)-benzenamine (4.5g) in 100 ml of methyl iodide is heated at reflux for three days. Theresultant precipitate is collected by filtration and recrystallized fromacetonitrile/benzene to yield 6 g of the title compound, melting point199° C.

Anal. Calc'd. for C₁₅ H₁₄ NOS₂ . I: C, 43.37; H, 3.40; N, 3.37; S,15.44; I, 30.57. Found: C, 45.53; H, 3.39; N, 3.48; S, 15.18; I, 30.68.

PREPARATION 5 N-Methyl-N-(5-nitro-1,3-benzodithiol-2-ylidene)benzaminiumiodide

A. n-(5-nitro-1,3-benzodithiol-2-ylidene)benzenamine

A solution of 5-nitro-1,2,3-benzothiadiazole (4.6 g) in 50 ml ofphenylisothiocyanate is heated at 220° C under an inert atmosphere untilthe evolution of nitrogen ceases (approximately three hours). The excessphenylisothiocyanate is removed in vacuo and the resultant residuechromatographed on 1000 ml of silica gel eluting with methylenechloride/pentane (1:4). The fractions containing the desired product arecombined and concentrated in vacuo. The resultant solid isrecrystallized from cyclohexane to yield 2.1 g of the title compound,melting point 136°-138° C.

Anal. Calc'd. for C₁₃ H₈ N₂ O₂ S₂ : C, 54.15; H, 2.80; N, 9.72; S,22.24. Found: C, 54.14; H, 2.66; N, 9.84; S, 22.50.

B. n-methyl-N-(5-nitro-1,3-benzodithiol-2-ylidene)benzaminium iodide

A solution of N-(5-nitro-1,3-benzodithiol-2-ylidene)benzenamine (5 g)and methyl iodide (20 ml, excess) in benzene (100 ml) is heated atreflux for 2.5 weeks. The resulting slurry is filtered and rechargedwith methyl iodide every three days. The combined collected precipitateis recrystallized from acetonitrile/benzene to yield 4.0g of the titlecompound, melting point 210° C.

Anal. Calc'd. for C₁₄ H₁₁ N₂ O₂ S₂ . I: C, 39.08; H, 2.58; N, 6.51; S,14.90; I, 29.49. Found: C, 39.36; H, 2.60; N, 6.74; S, 15.15; I, 29.68.

PREPARATION 6N-Methyl-N-[5-(trifluoromethyl)-1,3-benzodithiol-2-ylidene]-benzminiumiodide

A. n-[5-(trifluoromethyl)-1,3-benzodithiol-2-ylidene]benzenamine

Anal. Calc'd. for C₁₂ H₁₆ N₂ S₂ · 2HCl · H₂ O: C, 41.98; H, 5.87; N,8.16; S, 18.68; Cl, 20.65. Found: C, 41.76; H, 6.17; N, 7.96; S, 18.48;Cl, 20.37.

EXAMPLE 19 N'-(1,3-Benzodithiol-2-ylidene)-N,N-dibutyl-1,2-ethanediamine

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), N,N-dibutyl-1,2-ethanediamine (5.16g) and anhydrous sodiumcarbonate (1.59g) in 200 ml of anhydrous dimethylformamide is heated at120° C for two hours and left

A solution of 5-(trifluoromethyl)-1,2,3-benzothiadiazole (5 g) in 50 mlof phenylisothiocyanate is heated at reflux under an inert atmosphereuntil the evolution of nitrogen ceases (approximately 3 hours). Theexcess phenyl isothiocyanate is removed by distillation. The residue ischromatographed on 1000 ml of silica gel eluting withpentane/dichloromethane (4:1). Fractions containing the desired productare combined and concentrated in vacuo. The resultant solid isrecrystallized from hexane to yield 4 g of the title compound, meltingpoint 122°-123° C.

Anal. Calc'd. for C₁₄ H₈ F₃ NS₂ : C, 54.01; H, 2.59; N, 4.50; S, 20.59;F, 18.31. Found: C, 54.22; H, 2.45; N, 4.52; S, 20.74; F, 18.11.

B.n-methyl-N-[5-(trifluoromethyl)-1,3-benzodithiol-2-ylidene]-benzenaminiumiodide

A solution ofN-[5-(trifluoromethyl)-1,3-benzodithiol-2-ylidene]benzenamine (2.4 g)and methyl iodide (20 ml, excess) in 100 ml of benzene is heated atreflux for 2.5 weeks. The reaction mixture is filtered and rechargedwith methyl iodide every three days. The combined precipitates (3.3g)are recrystallized from acetonitrile/benzene. The recrystallized productis dried in vacuo at 100° C for three days to yield 3.0g of the titlecompound, melting point 161°-164° C.

Anal. Calc'd. for C₁₅ H₁₁ NS₂ F₃ I . 0.5 C₆ H₆ : C, 43.90; H, 2.87; N,2.84; S, 13.02; I, 25.79. Found: C, 43.84; H, 2.68; N, 2.91; S, 13.22;I, 25.90.

PREPARATIONS 7-10

Following the procedure of preparation 1, but substituting the compoundlisted in column I for 5-chloro-1,2,3-benzothiadiazole yields thecompound listed in column II.

    ______________________________________                                        Column I              Column II                                               ______________________________________                                        7.   5-methyl-1,2,3- 5,N-dimethyl-N-                                               benzothiadiazole                                                                              phenyl-1,3-benzodithiol-                                                      2-iminium iodide                                         8.   5-amino-1,2,3   5-amino-N-methyl-N-                                           benzothiadiazole                                                                              phenyl-1,3-benzodithiol-                                                      2-iminium iodide                                         9.   5-hydroxy-1,2,3-                                                                              5-hydroxy-N-methyl-N-                                         benzothiadiazole                                                                              phenyl-1,3-benzodithiol-                                                      2-iminium iodide                                         10.  5-bromo-1,2,3-  5-bromo-N-methyl-N-                                           benzothiadiazole                                                                              phenyl-1,3-benzodithiol-                                                      2-iminium iodide                                         ______________________________________                                    

The following examples are specific embodiments of this invention.

EXAMPLE 1 [(1,3-Benzodithiol-2-ylidene)amino]acetic acid, ethyl ester

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(3.85g), 2-amino-acetic acid ethyl ester, hydrochloride (1.40g), andanhydrous potassium carbonate (1.38g) in 200 ml of anhydrousdimethylformamide is heated at 120° C under a nitrogen atmosphere fortwo hours. The reaction mixture is then poured into two liters ofdistilled water and extracted with three 300 ml portions of benzene. Thecombined benzene extracts are dried over anhydrous sodium sulfate andconcentrated in vacuo to yield 2.5g of crude product, which ischromatogrphed on 600 ml of silica gel, eluting first withpentane/dichloromethane (1:1) and finally with dichloromethane. Theproduct with R_(f) =0.32 (silica gel, 2% ethyl acetate/dichloromethane)is recrystallized from pentane to yield 1900 mg of the title compound,melting point 88°-89° C.

Anal. Calc'd. for C₁₁ H₁₁ NO₂ S₂ : C, 52.15; H, 4.38; N, 5.53; S, 25.31.Found: C, 52.38; H, 4.45; N, 5.53; S, 25.13.

EXAMPLE 2 3-[(1,3-Benzodithiol-2-ylidene)amino]propanoic acid, ethylester

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methyl benzaninium iodide(11.55g), 3-aminopropanoic acid, ethyl ester hydrochloride (4.61g) andanhydrous sodium carbonate (3.18g) in 400 ml of anhydrousdimethylformamide is heated at 120° C under a nitrogen atmosphere for 2hours. The reaction mixture is poured into 3 liters of distilled waterand extracted with three 500 ml portions of benzene. The combinedbenzene extracts are dried over anhydrous sodium sulfate andconcentrated in vacuo to yield an oil. The oil is chromatographed on1000 ml of silica gel, eluting first with pentane/dichloromethane (1:1)and finally dichloromethane. The produce obtained with R_(f) =0.35(silica gel/2% ethyl acetate:dichloromethane) is recrystallized frompentane to yield 2.3g of the title compound, melting point 61°--62° C.

Anal. Calc'd. for C₁₂ H₁₃ NO₂ S₂ : C, 53.91; H, 4.90; N, 5.24; S, 23.99;Found: C, 53.80; H, 4.89; N, 5.23; S, 23.90.

EXAMPLE 3 [(1,3-Benzodithiol-2ylidene)amino]acetic acid

A solution of [(1,3-benzodithiol-2-ylidene) amino]-acetic acid ethylester (2.5g, prepared as described in Example 1) and potassium hydroxide(550 mg) in 500 ml of anhydrous methyl alcohol is stirred at roomtemperature for 120 hours. The reaction mixture is then concentrated invacuo. The resultant solid residue is triturated with diethyl either toremove unreacted starting material. The undissolved residue is thendissolved in 50 ml of water and filtered through Celite. The aqueoussolution is treated with 10% hydrochloric acid until the pH is 5. Theresultant precipitate is collected by filtration and dried in vacuo overphosphorous pentoxide at 60° C for about 16 hours. The dried solid isrecrystallized twice from ethyl acetate to yield 1.3g of the titlecompound, melting point 195°-200° C.

Anal. Calc'd. for C₉ H₇ NO₂ S₂ : C, 47.98; H, 3.13; N, 6.22; S, 28.47.Found: C, 48.22; H, 3.10; N, 6.26; S, 28.26.

EXAMPLE 4 3-[(1,3-Benzodithiol-2-ylidene)amino]propanoic acid

A solution of 3-[(1,3-benzodithiol-2ylidene)amino]-propanoic acid, ethylester (3.0g, prepared as described in Example 2) and sodium hydroxide(499 mg) in 120 ml of absolute ethanol is stirred at room temperaturefor 120 hours. The reaction mixture is concentrated in vacuo, and theresultant solid residue is washed with diethyl ether to remove unreactedstarting material. The crude reaction product is dissolved in 50 ml ofwater, filtered through Celite, and the aqueous solution is then treatedwith 10% hydrochloric acid until the pH is 5. The resultant precipitateis collected by filtration and dried in vacuo at 60° C overnight.Recrystallization of the dried product from n-pentyl alcohol yields 1.9gof the title compound, melting point 203-204° C.

Anal. Calc'd. for C₁₀ H₉ NO₂ S₂ : C, 50.19; H, 3.79; N, 5,85; S, 26.80.Found: C, 50.29; H, 3.99; N, 5.72; S, 26.77.

EXAMPLE 5 4-[(1,3-Benzodithiol-2-ylidene)amino]butanoic acid, ethylester

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), 4-aminobutanoic acid, ethyl ester, hydrochloride (5.04g) andanhydrous sodium carbonate (3.18g) in 300 ml of anhydrousdimethylformamide is heated at 130° C under a nitrogen atmosphere for 3hours. The reaction mixture was poured into 1000 ml of water andextracted with three 300 ml portions of benzene. The combined benzeneextracts are washed with two 500 ml portions of water, dried over sodiumsulfate, and concentrated in vacuo. The resultant yellow oil ischromatographed on silica gell (900 ml) using dichloromethane/petane(1:1) as eluent. The product with R_(f) =0.42 (silicagel/dichloromethane) is recrystallized from petane to yield 1.8g of thetitle compound, melting point 35°-36° C.

Anal. Calc'd. for C₁₃ H₁₅ NO₂ S₂ : C, 55.49; H, 5.37; N, 4.98; S, 22.79.Found: C, 55.60; H, 5.55; N, 5.03; S, 22.67.

EXAMPLE 6 [(1,3-Benzodithiol-2-ylidene)amino]butanoic acid

A solution of 4-[(1,3-benzodithiol-2-ylidene)amino]-butanoic acid, ethylester (3g, prepared as described in Example 5) and sodium hydroxide (427mg) in 80% aqueous ethanol (50 ml) is stirred at room temperature forseven days. The reaction mixture is concentrated in vacuo and theresidue triturated with two 50 ml portions of hot benzene. The solidresidue is dissolved in 100 ml of water, filtered through Celite, andthe filtrate treated with 10% hydrochloric acid until the pH is 4. Thesolid precipitate is collected by filtration and washed on the filterwith water. Recrystallization of the solid product from chloroformyields 1.3g of the title compound, melting point 140°-142° C.

Anal. Calc'd. for C₁₁ H₁₁ NO₂ S₂ : C, 52.15; H, 4.38; N, 5.53; S, 25.31.Found: C, 52.27 H, 4.43; N, 5.73; S, 25.02.

EXAMPLE 7 3-[(1,3-Benzodithiol-2-ylidene)amino]propanoic acid, methylester

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), 3-aminopropanoic acid, methyl ester hydrochloride (4.19g) andanhydrous sodium carbonate (3.18g) in 300 ml of anhydrousdimethylformamide is heated at 120° C under nitrogen for three hours.The reaction mixture is poured into water (1000 ml) and extracted withthree 200 ml portions of benzene. The combined benzene extracts arewashed with water and brine, dried over anhydrous sodium sulfate, andconcentrated in vacuo to yield 13.0g of crude product. This product ischromatographed on silica gel (1000 ml) eluting with 1) pentane (2000ml); 2) dichloromethane/pentane (4000 ml, 1:1); and 3) dichloromethane(6000 ml). The fractions containing the product with R_(f) =0.38 (silicagel/dichloromethane) are combined and concentrated in vacuo.

The resultant solid is recrystallized from pentane to yield 3.65g of thetitle compound, melting point 58°-60 ° C.

Anal. Calc'd. for C₁₁ H₁₁ NO₂ S₂ : C, 52.15; H, 4.38; N, 5.53; S, 25.31.Found: C, 52.43; H, 4.50; N, 5.45; S, 25.54.

EXAMPLE 8 3-[(1,3-Benzodithiol-2-ylidene)amino]propanoic acid,1-methylethyl ester

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), 3-aminopropanoic acid, isopropyl ester, hydrochloride (5.03g)and anhydrous sodium carbonate (3.18g) in 300 ml of anhydrousdimethylformamide is heated at 120° C under nitrogen for 3 hours. Thereaction mixture is poured into water (1000 ml) and extracted with three200 ml portions of benzene. The combined benzene extracts are washedwith water and brine, dried over anyhdrous sodium sulfate, andconcentrated in vacuo to yield 10.0 g of crude product. The crudeproduct is chromatographed on silica gel (1000 ml) eluting with 1)pentane (1000 ml); 2) pentane/dichloromethane (1.1, 4000 ml); and 3)dichloromethane (1000 ml). the fractions containing the product withR_(f) =0.3 (silica gel/dichloromethane) are concentrated and theresultant solid recrystallized from pentane to yield 2.2g of the titlecompound, melting point 60°-61° C.

Anal. Calc'd. for C₁₃ H₁₅ NO₂ S₂ : C, 55.49; H, 5.37; N, 4.98; S, 22.79.Found: C,55.21; H, 5.26; N, 4.91; S, 22.97.

EXAMPLE 9 3-[(1,3-Benzodithiol-2-ylidene)amino]propanoic acid, butylester

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), 3-aminopropanoic acid, n-butyl ester, hydrochloride (5.45g)and anhydrous sodium carbonate (3.18g) in 300 ml of anhydrousdimethylformamide is heated at 120° C under nitrogen for three hours.The reaction mixture is poured into water (1000 ml) and extracted withthree 200 ml portions of benzene. The combined benzene extracts arewashed with water and brine, dried over anhydrous sodium sulfate, andconcentrated in vacuo to yield 12g of crude product. the crude oil ischromatographed on silica gel (1000 ml), eluting with 1) pentane (2000ml), 2) dichloromethane/pentane (1:1, 4000 ml) and 3) dichloromethane(1000 ml). The fractions containing product with R_(f) =0.4 (silica gel,1% ethyl acetate, dichloromethane) are combined and concentrated invacuo. The resultant precipitate is collected by filtration at 4° C toyield 1.3g of the title compound which is an oil at room temperature.

Anal. Calc'd. for C₁₄ H₁₇ NO₂ S₂ : C, 56.92; H, 5.80; N, 4.74; S, 21.71.Found: C, 56.85; H, 5.93; N, 4.64; S, 21.79.

EXAMPLE 10 3-[(5-Chloro-1,3-benzodithiol-2-ylidene)amino]butanoic acid,ethyl ester

A solution of 5-chloro-N-methyl-N-phenyl-1,3-benzodithiol-2-iminiumiodide (12.59g), 4-aminobutanoic acid, ethyl ester, hydrochloride(5.02g), and anhydrous sodium carbonate (3.18g) in 300 ml of anhydrousdimethylformamide is heated at 120° C under nitrogen for three hours.The reaction mixture is poured into water (1000 ml) and extracted withthree 200 ml portions of benzene. The combined benzene extracts arewashed with water and brine, dried over sodium sulfate, and concentratedin vacuo. The resultant crude product is chromatographed on silica gel(1000 ml) eluting with 1) pentane (1000 ml), 2) pentane/dichlormethane(1:1, 4000 ml) and 3) dichloromethane (9000 ml). The fractionscontaining product with R_(f) =0.4 (silica gel, 1% ethylacetate/dichloromethane) are concentrated in vacuo. The resultant solidis recrystallized from pentance to yield 3.02g of the title compound,melting point 60°-61° C.

Anal. Calc'd. for C₁₃ H₁₄ ClNO₂ S_(2:) C, 49.44; H, 4.47; N, 4.43; Cl,11.22; S, 20.30. Found: C, 49.71; H, 4.52; N, 4.59; Cl, 11.42; S, 20.54.

EXAMPLE 11 3-[(1,3-Benzodithiol-2-ylidene)amino]butanoic acid, methylester

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), 4-aminobutanoic acid, methyl ester, hydrochloride (4.61g) andanhydrous sodium carbonate (3.18g) in 300 ml of anhydrousdimethylformamide is heated at 120° C under nitrogen for 3 hours. Thereaction mixture is poured into water (1400 ml) and extracted with three200 ml portions of benzene. The combined benzene extracts are washedwith water and brine, dried over sodium sulfate, and concentrated invacuo. The resultant oil is chromatographed on silica gel (1000 )eluting with 1) pentant (2000 ml), 2) pentane/dichloromethane (1:1, 4000ml) and 3) dichloromethane (9000 ml). The fractions containing productwith R_(f) =0.4 (silica gel, 1% ethyl acetatedichloromethane) arecombined and concentrated in vacuo. The resultant solid isrecrystallized from pentane to yield 1.2g of the title compound, meltingpoint 78°-80° C. A second crop gives 1.6g, melting point 78°-80° C.

Anal. Calc'd. for C₁₂ H₁₃ NO₂ S₂ : C, 53.91; H, 4.90; N, 5.24; S, 23.99.Found: C,53.66; H, 5.18; N, 5.04; S, 23.94.

EXAMPLE 12 3-[(,3-Benzodithiol-2-ylidene)amino]butanoic acid,1-methylethyl ester

A solution of N-(1,3-benzodithiol-2-N-methylbenzaminium iodide (11.55g),4-aminobutanoic acid, isopropyl ester, hydrochloride (5.45g) andanhydrous sodium carbonate (3.18g) in 300 ml of anhydrousdimethylformamide is heated at 120° C under nitrogen for 3 hours. Thereaction mixture is poured into water (1400 ml) and extracted with three200 ml portions of benzene. The combined benzene extracts are washedwith water and brine, dried over sodium sulfate, and concentrated invacuo. The resultant oil is chromatographed on silica gel (1000 ml)eluting with 1) pentane (2000 ml), 2) pentane-dichloromethane (4000 ml,1:1) and 3) dichloromethane (9000 ml). The fractions containing productwith R_(f) =0.35 (silica gel; 1% ethylacetate/dichloromethane) arecombined and concentrated in vacuo. The resultant solid isrecrystallized from pentane to yield 3.1g of the title compound, meltingpoint 44° C.

Anal. Calc'd. for C₁₄ H₁₇ NO₂ S₂ : C, 56.92; H, 5.80; N, 4.74; S, 21.71.Found: C, 56.76; H, 5.68; N, 4.65; S, 21.59.

EXAMPLE 13 3-[(1,3-Benzodithiol-2-ylidene)amino]butanoic acid, butylester

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbanzaminium iodide(11.55g), 4-aminobutanoic acid, n-butyl ester, hydrochloride (5.87g) andanhydrous sodium carbonate (3.18g) in 300 ml of anhydrousdimethylformamide is heated at 120° C under nitrogen for 3 hours. Thereaction mixture is poured into water (1400 ml) and extracted with three200 ml portions of benzene. The combined benzene extracts are washedwith water and brine, dried over sodium sulfate, and concentrated invacuo. The resultant oil is chromatographed on silica gel (1000 ml)eluting with 1) pentane (2000 ml), 2) pentane/dichloromethane (1:1, 4000ml) and 3) dichloromethane (6000 ml). The fractions containing productwith R_(f) =0.45 (silica gel, 1% ethyl acetate/dichloromethane) arecombined and concentrated. The resultant oil is dissolved in pentane andchilled to -20° C. The resultant solid precipitate is collected byfiltration at 0° C to yield 3.5g of the title compound, which is an oilat room temperature.

Anal. Calc'd. for C₁₅ H₁₉ NO₂ S₂ : C, 58.22; H, 6.19; N, 4.53; S, 20.72.Found: C, 58.11; H, 6.01; N, 4.41; S, 20.52.

EXAMPLE 14 3-[(5-Chloro-1,3-benzodithiol-2-ylidene)amino]propanoic acid,ethyl ester

A solution of 5-chloro-N-methyl-N-phenyl-1,3-benzo-dithiol-2-iminiumiodide (9.97g), 3-aminopropanoic acid, ethyl ester, hydrochloride(3.68g) and anhydrous sodium carbonate (2.54g) in 250 ml of anhydrousdimethylformamide is heated at 120° C under nitrogen for 3 hours, thenleft stirring at room temperature for 2 days. The reaction mixture ispoured into water (1400 ml) and extracted with three 200 ml portions ofdichloromethane. The combined dichloromethane extracts are washed withthree 100 ml portions of water, dried over sodium sulfate, andconcentrated in vacuo. The resultant oil is chromatographed on silicagel (1000 ml), eluting with dichloromethane/pentane (1:1). The fractionscontaining product with R_(f) =0.25 (silica gel, dichloromethane) areconcentrated and the resultant solid recrystallized twice from pentaneto yield 1.1g of the title compound, melting point 64°-65° C.

Anal. Calc'd. for C₁₂ H₁₂ ClNS₂ O₂ : C, 47.75; H, 4.01; N, 4.64; Cl,11.75; S, 21.25. Found: C, 47.97; H, 4.01; N, 4.74; Cl, 12.01; S, 20.99.

EXAMPLE 15N'-(1,3-Benzodithiol-2-ylidene)-N,N-dimethyl-1,2-ethanediamine and thedihydrochloride salt thereof

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(3.85g), dimethylethylenediamine (880 mg), and anhydrous sodiumcarbonate (530 mg) in 100 ml of dry dimethylformamide is heated at 100°C for two hours, then left stirring at room temperature overnight. Thereaction mixture is poured into 800 ml of water and the resultantprecipitate is collected by filtration. The white solid contains threemajor components by thin layer chromatography (silica gel/chloroform).The solid is dissolved in 75 ml of hexane and purified by columnchromatography (200 ml of silica gel), eluting with 1) benzene (1000ml), 2) chloroform (1000 ml) and 3) 10% methanol/chloroform. The solidproduct obtained by concentration of the fractions eluted withmethanol/chloroform are recrystallized from pentane to yield 1.2g of thetitle compound, melting point 70°-72° C.

Anal. Calc'd. for C₁₁ H₁₄ N₂ S₂ : C, 55.42; H, 5.92; N, 11.75; S, 26.90.Found: C, 55.67; H, 6.04; N, 11.46; S, 26.83.

EXAMPLE 16N'-(1,3-Benzodithiol-2-ylidene)-N,N-dimethyl-1,2-ethanediamine,hydrochloride (1:2)

A solution ofN'-(1,3-benzodithiol-2-ylidene)-N,N-dimethyl-1,2-ethanediamine (2.0g,prepared as described in Example 15) in 100 ml of diethyl ether istreated dropwise with ethereal hydrogen chloride until precipitation iscomplete. The white solid thus obtained is filtered, washed with diethylether, and recrystallized from acetonitrile. The recrystallized materialwas filtered and washed with diethyl ether before drying overphosphorous pentoxide for 4 days. Analysis of this product (1.4g)indicates it to be a mixture of mono- and dihydrochloride. The productis recrystallized from ethanol with the addition of 5 ml of etheralhydrogen chloride. The recrystallized solid is filtered under nitrogen,washed with diethyl ether, and dried under nitrogen at atmosphericpressure to yield 1.2g of the title compound, melting point 218°-220° C.

Anal. Calc'd. for C₁₁ H₁₄ N₂ S₂ · 2 HCl · H₂ O: C, 40.12; H, 5.47; N,8.51; S, 19.47; Cl, 21.53. Found: C, 39.85; H, 5.52; N, 8.43; S, 19.41;Cl, 21.48.

EXAMPLE 17N'-(1,3-Benzodithiol-2-ylidene)-N,N-dimethyl-1,3-propanediamine

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methyl benzaminium iodide(11.55g), anhydrous sodium carbonate (1.59g) and3-dimethylaminopropylamine (3.06g) in 200 ml of anhydrousdimethylformamide is heated under a nitrogen atmosphere at 120° C fortwo hours and left stirring at room temperature for about 16 hours. Thereaction mixture is poured into water (2 liters) and extracted threetimes with 500 ml portions of benzene. The combined benzene extracts aredried over anhydrous sodium sulfate and concentrated in vacuo to yieldan oil. This oil is chromatographed on 500 ml of silica gel and elutedwith benzene (2 liters), chloroform (2 liters) and finally 10%methanol/chloroform (1 liter). The oil obtained from the 10%methanol/chloroform elution is dissolved in 100 ml of anhydrous diethylether and treated with ethereal hydrogen chloride until precipitation iscomplete. The precipitate is filtered and recrystallized fromacetonitrile to yield 8g of dihydrochloride, melting point 201°-205° C.This dihydrochloride is dissolved in 100 ml water and treated with 100ml of 5% sodium bicarbonate solution. The solution is extracted with 100ml of dichloromethane. The organic layer is dried over sodium sulfateand concentrated. The solid thus obtained is recrystallized from pentaneat -30° C to yield 4g of the title compound, melting point 45.5°-46.5°C. Removal of water from the molecule returns the compound to an oil.Water is needed in the lattice structure for crystallization.

Anal. Calc'd. for C₁₂ H₁₆ N₂ S₂ . 3/4 H₂ O: C, 54.20; H, 6.63; N, 10.53;S, 24.12. Found: C, 54.22; H, 6.34; N, 10.40; S, 24.16.

EXAMPLE 18N'-(1,3-Benzodithiol-2-ylidene)-N,N-dimethyl-1,3-propanediamine,hydrochloride (1:2)

A solution ofN'-(1,3-benzodithiol-2-ylidene)-N,N-dimethyl-1,3-propenediamine (3.0g,prepared as described in Example 17) in 100 ml of anhydrous diethylether is treated dropwise with ethereal hydrogen chloride untilprecipitation is completed. The resultant solid is collected byfiltration under a nitrogen atmosphere, wwashed several times withanhydrous diethyl ether and recrystallized twice from acetonitrile. Therecrystallized product is washed with anhydrous diethyl ether and driedat atmospheric pressure under a slow stream of nitrogen to yield 3.1g ofthe title compound, melting point 188°-190° C. stirring at roomtemperature overnight. The reaction mixture is poured into water (2liters) and extracted three times with 500 ml portions of benzene. Thecombined benzene layers are dried over anhydrous sodium sulfate andconcentrated. The resultant oil is chromatographed on 500 ml of silicagel eluting with benzene (2 liters), chloroform (2 liters) and finally10% methanol/chloroform (2 liters). The oil obtained from the elutionwith 10% methanol/chloroform is dissolved in ether, treated withethereal hydrogen chloride, and filtered under nitrogen. Thishygroscopic solid is dissolved in 5% sodium bicarbonate solution andextracted with dichloromethane. The dichloromethane layer is dried overanhydrous sodium sulfate and concentrated. The resultant oil isdissolved in 15 ml of pentane, treated with charcoal, and filtered. Thepentane solution was cooled to -78° C in a dry ice acetone bath. After24 hours, the white precipitate is quickly filtered and transferred to aflask whereup the product is returned to an oil. The oil is dried invacuo at room temperature overnight to yield 2g of the title compound.

Anal. Calc'd. for C₁₇ H₂₆ N₂ S₂ : C, 63.31; H, 8.13; N, 8.69; S, 19.88.Found: C, 63.55; H, 8.35; N, 8.59; S, 19.90.

EXAMPLE 20N'-(1,3-Benzodithiol-2-ylidene)-N,N-dibutyl-1,2-ethanediamine,hydrochloride (1:2)

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methyl-benzaminium iodide(11.55g), N,N-dibutyl-1,3-ethanediamine (5.16g) and anhydrous sodiumcarbonate (1.59g) in 200 ml of anhydrous dimethylformamide is heated at120° C under a nitrogen atmosphere for 2 hours, then left stirring atroom temperature overnight. The mixture is poured into water (400 ml)and extracted three times with 200 ml portions of benzene. The combinedbenzene layers are dried over anhydrous sodium sulfate and concentratedin vacuo. The resultant oil is purified by column chromatography (600 mlsilica gel) eluting with benzene (200 ml) and finally chloroform (400ml). The oil obtained from the chloroform elution is dissolved in 200 mlof anhydrous diethyl ether and treated dropwise with ethereal hydrogenchloride until precipitation is complete. The resultant hygroscopicsolid is collected by filtration under nitrogen and recrystallized twicefrom isopropyl alcohol. The product thus obtained is dried atatmospheric pressure over anhydrous phosphorous pentoxide for four daysto yield 1.16g of the title compound, melting point 145-147° C.

Anal. Calc'd. for C₁₇ H₂₆ N₂ S₂ . 2HCl: C, 49.38; H, 7.31; N, 6.78; S,15.51; Cl, 17.15. Found: C, 49.61; H, 7.63; N, 6.81; S, 15.64; Cl,17.06.

EXAMPLE 21

2,2'-[[3-[(1,3-Benzodithiol-2-ylidene)amino]propyl]imino]bisethanol,hydrochloride (1:2)

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaninium iodide(11.55g), N-(3-aminopropyl)-diethanolamine (4.8g) and anhydrous sodiumcarbonate (1.59g) in 200 ml of anhydrous dimethylformamide is heated at120° C for two hours under a nitrogen atmosphere. The reaction mixtureis poured slowly into vigorously stirring ice/water. The mixture is leftstirring at 4° C for two hours; however, no precipitation results. Themixture is extracted with three 500 ml portions of benzene. The combinedbenzene extracts are dried over anhydrous sodium sulfate andconcentrated. The resultant oil contains three major products by thinlayer chromatography [silica gel, dichloromethane/methanol (9:1)solvent, R_(f) =0.1, 0.5, 0.6]. Initial purification is effected bycolumn chromatography with silica gel (750 ml). Elution with benzenegives the products with R_(f) =0.5 and R_(f) =0.6. Elution withmethylene chloride/methanol (7:3) gives the product with R_(f) =0.1.This oil is dissolved in 200 ml of anhydrous diethyl ether and treateddropwise with ethereal hydrogen chloride until precipitation iscomplete. The hygroscopic solid thus obtained is collected by filtrationunder nitrogen and recrystallized three times from isopropylalcohol/methanol (95:5) to yield 1.6g of the title compound, meltingpoint 130-135° C.

Anal. Calc'd. for C₁₄ H₂₀ N₂ O₂ S₂ . 2HCl . H₂ O: C, 41.68; H, 6.00; N,6.94; Cl, 17.58; S, 15.90. Found: C, 41.87; H, 5.74; N, 6.68; Cl, 17.75;S, 16.06.

EXAMPLE 22 N-(1,3-Benzodithiol-2-ylidene)-1-piperidineethanamine,hydrochloride (1:2)

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), N-(2aminoethyl)piperidine (3.84g) and anhydrous sodiumcarbonate (1:59g) in 200 ml of anhydrous dimethylformamide is heated at120° C for two hours and left stirring at room temperature overnight.The reaction mixture is poured into 4 liters of water and extractedthree times with 300 ml portions of benzene. The combined benzene layersare dried over anhydrous sodium sulfate and concentrated. The resultantoil is chromatographed on 500 ml of silica gel eluting with benzene (2liters), chloroform (2 liters), and finally 10% methanol/chloroform (2liters). The solid product obtained from the final elution with 10%methanol/chloroform is recrystallized from pentane. Thisrecrystallization produces a crystalline material which contains twospots by thin layer chromatography (10% methanol/dichloromethane, silicagel). Further purification by recrystallization or column chromatographyis unsuccessful. The impure material is dissolved in diethyl ether andtreated with ethereal hydrogen chloride until precipitation is complete.The hygroscopic solid is filtered under nitrogen, washed with diethylether, and recrystallized from acetontrile. Attempts to dry the samplein vacuo result in the loss of HCl molecules. The procuct is air driedover phosphorous pentoxide to yield 5.3g of the title compound, meltingpoint 186-186.5° C (dec.).

Ana. Calc'd for C₁₄ H₁₈ N₂ S₂.2HCL.1/2 H₂ O: C, 46.66; H, 5.87; N, 7.77;Cl, 17.80; S.19.68. Found: C, 46.58H, 5.73; N, 7.77; Cl, 17.87; S,19.87.

EXAMPLE 23

N-(1,3-Benzodithiol-2-ylidene)-1-piperidineethanamine

A solution of N-(1,3-benzodithiol-2-ylidene)-1-piperidineethanamine,hydrochloride (1:2) (3.2g prepared as described in Example 22) in 50 mlof water is treated with 50 ml of 5% sodium bicarbonate solution andextracted with 100 ml of dichloromethane. After drying over anhydroussodium sulfate, the dichloromethane solution if concentrated in vacuo toyield a yellow oil which solidifices upon standing. The solid product isrecrystallized from pentane to yield 2.4g of product, melting point70-74° C. It becomres apparent after several attempts to dry the samplein vacuo that the sample is a hydrate. Drying over phosphorous pentoxideproduces an oil which immediately solidifies upon exposure to air.

Anal. Calc'd. for C₁₄ H₁₈ N₂ S₂ . H₂ O: C, 56.72; H, 6.80; N, 9.44; S,21.63. Found: C, 56.72; H, 6.74; N, 9.15; S, 21.82.

EXAMPLE 24N-(5-Chloro-1,3-benzodithiol-2-ylidene)-1-piperidineethanamine

A solution of 5-chloro-N-methyl-N-phenyl-1,3-benzodithiol-2-iminiumiodide (8.39g), N-(2-aminoethyl)piperidine (2.56g) and anhydrous sodiumcarbonate (1.06g) in 200 ml of anhydrous dimethylformamide is heated at120° C under a nitrogen atmosphere for three hours. The reaction mixtureis poured into 1000 ml of water and extracted with three 300 ml portionsof dichloromethane. The combined organic extracts are washed with two500 ml portions of water, dried over anhydrous sodium sulfate, andconcentrated in vacuo to yield an oil. This oil is chromatographed onsilica gel (1000 ml) eluting with (1) pentane (1000 ml), (2) chloroform(1000 ml), and finally methanol/chloroform (1:4, 2000 ml). The solidproduct from elution (3) is recrystallized from pentane to yield 4g ofthe title compound, melting point 42-44° C.

Anal. Calc'd. for C₁₄ H₁₇ ClN₂ S₂ : C, 53.74; H, 5.48; N, 8.95; Cl,11.33; S, 20.50. Found: C, 54.03; H, 5.46; N, 9.05; Cl, 11.03; S, 20.32.

EXAMPLE 25 N-(1,3-Benzodithiol-2-ylidene)-4-morpholineethanamine

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methyl-benzaminium iodide(3.85g), N-(aminoethyl)morpholine (1.30g) and anhydrous sodium carbonate(530 mg) in 100 ml of dry dimethylformamide is heated at 100° C for 2hours, then left stirring at room temperature for about 16 hours. Thereaction mixture is poured into 1000 ml of water and extracted threetimes with benzene. After drying over sodium sulfate, the combinebenzene extracts are concentrated to yield an oil which consisted ofthree major components by thin layer chromatography (silica gel/10%methanol/chloroform. The oil is dissolved in 50 ml of hexane andpurified initially by column chromatography (200 ml silica gel) using(1) benzene (1000 ml), (2) chloroform (1000 ml), and (3) 10%methanol/chloroform. The solid product obtained by concentration of thefactions eluted with 10% methanol/chloroform is recrystallized frompentane after treating with charcoal to yield 1.7g of the titlecompound, melting point 75-76° C.

Anal. Calc'd. for C₁₃ H₁₆ N₂ S₂ O₂ O: C, 55.68; H, 5.75; N, 9.99; S,22.87. Found: C, 55.82; H, 5.90; N, 9.92; S, 22.93.

EXAMPLE 26 N-(1,3-Benzodithiol-2-ylidene)-4-morpholineethanamine,hydrochloride (1:2)

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), N-(2-aminoethyl)morpholine (3.90g) and anhydrous sodiumcarbonate (1.59g) in 100 ml of anhydrous dimethylformamide is heatedunder a nitrogen atmosphere at 120° C for two hours and left stirring atroom temperature for about 16 hours. The reaction mixture is poured intowater (4 liters) and extracted three times with 500 ml portions ofbenzene. The combined organic layers are dried over anhydrous sodiumsulfate and concentrated under reduced pressure. The resultant oil ischromatographed on 600 ml of silica gel eluting with benzene (2 liters)and finally chloroform (4 liters). The oil obtained from elution withchloroform is dissolved in 100 ml of diethyl ether and treated withethereal hydrogen chloride until precipitation is completed. The solidis filtered under nitrogen, washed with diethyl ether, andrecrystallized from ethanol. Attempts to dry the sample in vacuo resultin loss of HCl molecules. The product is air dried over phosphorouspentoxide to yield 9.1g of the title compound, melting point 211-214° C.

Anal. Calc'd. for C₁₃ H₁₆ N₂ OS₂ . 2 HCl . H₂ O: C, 42.05; H, 5.43 ,N7.54; Cl, 19.09; S, 17.27. Found: C, 42.23; H, 5.54; N, 7.61; Cl, 19.36;S, 17.38.

EXAMPLE 27 N-(1,3-Benzodithiol-2-ylidene)-4-morpholinepropanamine

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(11.55g), N-(3-aminopropyl)-morpholine (4.32g) and anhydrous sodiumcarbonate (1.59g) in 200 ml of anhydrous dimethylformamide is heated at120° C under a nitrogen atmosphere for two hours. The reaction mixtureis poured into 1000 ml of ice-water and left at 4° C for two hours. Theprecipitate is collected by filtration. The solid product is dissolvedin dichloromethane, dried over anhydrous sodium sulfate, andconcentrated in vacuo to yield 3g of crude product. The solid isrecrystallized twice from pentane to yield 1.8g of the title compound,melting point 66-68° C.

Anal. Calc'd. for C₁₄ H₁₈ N₂ OS₂ : C, 57.11; H, 6.16; N, 9.51; S, 21.78.Found: C, 56.96; H, 5.85; N, 9.58; S, 21.51.

EXAMPLE 281-[3-[(1,3-Benzodithiol-2-ylidene)amino]propyl]-2-pyrrolidinone

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(3.85g), N-(3-aminopropyl)-2-pyrrolidinone (1.42g) and anydrous sodiumcarbonate 8530 mg) in 100 ml of anhydrous dimethylformamide is heated at120° C for two hours. The reaction mixture is poured into one liter ofice-water and after two hours extracted three times with 200 ml portionsof benzene. The combined benzene extracts are dried over anhydroussodium sulfate and concentrated in vacuo. The resultant semi-solid isrecrystallized twice from hexane/benzene (90:10) to yield 1.2g of thetitle compound, melting point 101-104° C.

Anal. Calc'd. for C₁₄ H₁₆ N₂ OS₂ : C, 57.50; H, 5.52; N, 9.58; S, 21.93.Found: C, 57.62; H, 5.51; N, 9.70; S, 21.67.

EXAMPLE 291-[3-[(5-Chloro-1,3-benzodithiol-2-ylidene)amino]propyl]-2-pyrrolidinone

A solution of 5-chloro-N-methyl-N-phenyl-1,3-benzodithiol-2-iminiumiodide (8.39g), N-(3-aminopropyl)-2-pryrrolidinone (2.84g) and anhydroussodium carbonate (1.06g) in 200 ml of anhydrous dimethylformamide isheated at 120° C under a nitrogen atmosphere for the three hours. Thereaction mixture is poured into 1000 ml of water and extracted withthree 400 ml portions of dichloromethane. The combined organic extractsare washed with two 150 ml portions of water, dried over anhydroussodium sulfate, and concentrated in vacuo to yield an oil. This oil ischromatographed (900 ml of silica gel) eluting with (1) pentane (2000ml), (2) pentane/dichloromethane (1:1, 1000 ml), (3) dichloromethane(1000 ml), (4) ethylacetate/dichloromethane (2:8, 1000 ml), and finally(5) methanol/ethyl acetate/dichloromethane (1:2:7, 3000 ml). The oilobtained from elution (5) is dissolved in 120 ml ofhexane/dichloromethane (6:1) and cooled to -40° C. The resultant solidis filtered. This solid is then recrystallized from cyclohexane to yield2.6g of the title compound, melting point 97°-97.5° C.

Anal. Calc'd. for C₁₄ H₁₅ ClN₂ S₂ O: C, 51.44; H, 4.63; N, 8.57; S,19.62; Cl, 10.85. Found: C, 51.49; H, 4.33; N, 8.67; S, 19.60; Cl,10.66.

EXAMPLE 30 1-[(1,3-Benzodithiol-2-ylidene)amino]-2-pyrrolidinone

A mixture of 16.0g of N-(1,3-benzodithol-2-ylidene)-N-methylbenzaminiumiodide, 5.8g of N-aminopyrrolidinone·HCl and 4.5g of sodium carbonate isprepared in 120 ml of dimethylformamide. This mixture is heated at 120°C for 3 hours and then poured into water. The water mixrure is extractedwith three 300 ml portions of benzene and the benzene extracts arecombined and washed with water (500 ml), 5% HCl (500 ml) and brine (300ml). The benzene extract is then dried over sodium sulfate andconcentrated to yield an oil which crystallizes on cooling. The productis recrystallized from cyclohexane to yield 4.4g of the title compound,melting point 122°-124° C.

Anal. Calc'd. for: C, 52.77; H, 4.03; N, 11.19; S, 25.61. Found: C,52.85; H, 4.28; N, 11.07; S, 25.90.

EXAMPLE 31 N-(1,3-Benzodithiol-2-ylidene)-1H-indol-3-ethanamine

Tryptamine hydrochloride (1.87g), sodium carbonate (1.06g) andN-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide (3.85g) arecombined in 150 ml of anhydrous dimethylformamide and heated at 100° Cunder a nitrogen atmosphere for one hour. The reaction mixture is pouredinto 500 ml of water and the solid precipitate is collected byfiltration. This solid is dissolved in hot benzene/cyclohexane, treatedwith charcoal, filtered through Celite, and allowed to crystallize atroom temperature. A second recrystallization from cyclohexanebenzeneyields 2.4g of the title compound, melting point 149°-149.5° C.

Anal. Calc'd. for C₁₇ H₁₄ N₂ S₂ : C, 65.77; H, 4.55; N, 9.03; S, 20.66.Found: C, 65.96; H, 4.71; N, 9.30; S, 20.45.

EXAMPLE 32N-(1,3-Benzodithiol-2-ylidene)-5-methoxy-1H-indole-3-ethanamine

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(3.39g), 5-methoxytryptamine hydrochloride (2.0g), and anhydrous sodiumcarbonate (933 mg) in 100 ml of anhydrous dimethylformamide is heated at120° C under a nitrogen atmosphere for 2 hours. The reaction mixture ispoured into 1500 ml of ice-water. After stirring for 2 hours the slurryis filtered. The solid thus obtained is dissolved in dichloromethane,dried over anhydrous sodium sulfate, and concentrated. The resultantsolid is recrystallized twice from pentane/benzene (50:50) to yield 1.5gof the title compound, melting point 139°-139.5° C.

Anal. Calc'd. for C₁₈ H₁₆ N₂ S₂ O: C, 63.50; H, 4.74; N, 8.23; S, 18.84.Found: C, 63.32; H, 4.82; N, 8.00; S, 19.05.

EXAMPLE 33N-(1,3-Benzodithiol-2-ylidene)-6-fluoro-1H-indole-3-ethanamine

A solution of N-(1,3-benzodithiol-2-ylidene-N-methylbenzaminium iodide(4.32g), 6-fluorotryptamine (2.0g) and anhydrous sodium carbonate (595mg) in 100 ml of anhydrous dimethylformamide is heated at 120° C under anitrogen atmosphere for two hours. The reaction mixture is poured into500 ml of water and extracted with three 200 ml portions of benzene. Thecombined benzene extracts are dried over anhydrous sodium sulfate andconcentrated. The resultant solid is recrystallized twice fromdichloromethane/hexane to yield 1.45g of the title compound, meltingpoint 193° C.

Anal. Calc'd. for C₁₇ H₁₃ FN₂ S₂ : C, 62.17; H, 3.99; N, 8.53; F, 5.78;S, 19.53. Found: C, 62.44; H, 4.07; N, 8.62; F, 5.69; S, 19.38.

EXAMPLE 34N-(1,3-Benzodithiol-2-ylidene)-1-[(4-chlorophenyl)methyl]-1H-indole-3-ethanamine

Sodium hydride (50% dispersion in mineral oil; 155 mg) is slurried in 5ml of anhydrous 1,2-dimethoxyethane and treated dropwise withN-(1,3-benzodithiol-2-ylidene)-1H-indol-3-ethanamine (1g, prepared asdescribed in Example 30) in 5 ml of anhydrous 1,2-dimethoxyethane. Themixture is heated at reflux for 3 hours. A solution ofα,p-dichlorotoluene (520 mg) in 5 ml of anhydrous 1,2-dimethoxyethane isadded dropwise to the refluxing reaction mixture. Refluxing is continuedfor four hours after addition is complete. The reaction mixture is thenpoured into water (50 ml) and extracted with two 50 ml portions ofdichloromethane. The combined dichloromethane extracts are washed withwater and brine, dried over anhydrous sodium sulfate, and concentratedin vacuo. The resultant solid is chromatographed on silica gel (200 ml)eluting with dichloromethanepentane (1:1). The fractions containingproduct with R_(f) =0.8 (silica gel, dichloromethane) are concentrated.The solid thus obtained is recrystallized from hexane to yield 600 mg ofthe title compound, melting point 120°-121° C.

Anal. Calc'd. for C₂₄ H₁₉ ClN₂ S₂ : C, 66.27; H, 4.40; N, 6.44; S,14.74; Cl, 8.15.

Found: C, 666.50; H, 4.56; N, 6.43; S, 14.50; Cl, 8.19.

EXAMPLE 35N-(1,3-Benzodithiol-2-ylidene)-1-[(4-chlorophenyl)carbonyl]-1H-indole-3-ethanamine

Sodium hydride (57% dispersion in mineral oil; 408 mg) is slurried in 10ml of anhydrous 1,2-dimethoxyethane and treated dropwise withN-(1,3-benzodithiol-2-ylidene)-1H-indol-3-ethanamine (3g, prepared asdescribed in Example 30) in 15 ml of anhydrous 1,2-dimethoxyethane. Thereaction mixture is heated at reflux for 2 hours. A solution ofp-chlorobenzoyl chloride (1.69g) in 10 ml of anhydrous1,2-dimethoxyethane is added dropwise to the refluxing mixture.Refluxing is continued for an additional 4 hours. The reaction mixtureis then poured into water (100 ml) and extracted with three 50 mlportions of dichloromethane. The combined dichloromethane extracts arewashed with water and brine, dried over anhydrous sodium sulfate andconcentrated in vacuo. The residue is chromatographed on silica gel (500ml) eluting with dichloromethane/pentane (3:2). The fractions containingproduct with R_(f) =0.5 (silica gel; dichloromethane) are concentratedin vacuo. The solid thus obtained is recrystallized fromhexane/dichloromethane to yield 2.1g of the title compound, meltingpoint 135° C.

Anal. Calc'd. for C₂₄ H₁₇ ClN₂ OS₂ : C, 64.20; H, 3.82; N, 6.24; Cl,7.91; S, 14.28. Found: C, 64.24; H, 3.71; N, 6.19; Cl, 8.06; S, 14.15.

EXAMPLE 36N-(5-Chloro-1,3-benzodithiol-2-ylidene)-1H-indole-3-ethanamine

A solution of 5-chloro-N-methyl-N-phenyl-1,3-benzodithiol-2-iminiumiodide (8.39g), tryptamine hydrochloride (3.94g) and anhydrous sodiumcarbonate (2.12g) in 300 ml of anhydrous dimethylformamide is heated at130° C under a nitrogen atmosphere for 3 hours. After this time thereaction mixture is poured into 1 liter of water and extracted withthree 300 ml portions of benzene. The combined benzene extracts aredried over anhydrous sodium sulfate and then concentrated in vacuo toyield an oil. This oil is chromatographed on 600 ml of silica geleluting first with dichloromethane/pentane (1:1) and finallydichloromethane. The resultant product with R_(f) =0.36 (silicagel-dichloromethane) is recrystallized from dichloromethane/pentane toyield 840 mg of the title compound, melting point 145°-147° C.

Anal. Calc'd. for C₁₇ H₁₃ ClN₂ S₂ : C, 59.20; H, 3.80; N, 8.12; S,18.59; Cl, 10.28. Found: C, 59.48; H, 3.79; N, 8.07; S, 18.50; Cl,10.18.

EXAMPLE 373-[(1,3-Benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone

A solution of N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide(3.85g), N-aminorhodanine (1.48g) and anhydrous sodium carbonate (530mg) in 100 ml of anhydrous dimethylformamide is heated at 120° C under anitrogen atmosphere for 2 hours. The reaction mixture is then pouredinto 500 ml of ice/water and left stirring at 4° C for 2 hours. Theresultant precipitate is collected by filtration and washed severaltimes with cold water. The solid is air dried to yield 2.0g of crudeproduct. This product is recrystallized from dimethylformamide to yield1.9g of the title compound, melting point 295°-300° C.

Anal. Calc'd. for C₁₀ H₆ N₂ OS₄ : C, 40.25; H, 2.03; N, 9.39; S, 42.98.

Found: C, 40.27; H, 2.20; N, 9.30; S, 43.05.

EXAMPLE 383-[(1,3-Benzodithiol-2-ylidene)amino]-5-butylidene-3,5-dihydro-2-thioxo-4(5H)-thiazolone

A mixture of 1.5g of3-[(1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone (seeexample 37), butyraldehyde (100 ml), pyridine (1 ml) and acetic acid (2ml) is heated at reflux for 1 hour. The mixture is then diluted withhexane and the precipitate separated by filtration. The residue isrecrystallized from dioxane to yield 1.2 g of material. As this provedto be a mixture of product and starting material, the compound was mixedagain with butyraldehyde (100 ml) and pyridinium acetate (3 ml) andheated at reflux for 24 hours. Worked up as before and crystallized fromamyl alcohol the yield of the title compound is 900 mg, melting point236°-238° C.

Anal. Calc'd. for C₁₄ H₁₂ N₂ OS₄ : C, 47.70; H, 3.43; N, 7.95; S, 36.38.Found: C, 47.58; H, 3.40; N, 7.69; S, 36.28.

EXAMPLE 393-[(5-Chloro-1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone

A mixture of the methiodide of5-chloro-N-methyl-N-phenyl-1,3-benzodithiol-2-iminium iodide (1.9 g),sodium carbonate (121 mg), N-aminorhodanine (338 mg) anddimethylformamide (20 ml) is heated at 50° C for 3 hours. The mixture ispoured into water and the precipitate which forms is filtered and washedwith water. The product is recrystallized from dimethylformamide toyield 600 mg of the title compound, melting point 312°-314° C.

Anal. Calc'd. for C₁₀ H₅ ClN₂ OS₄ : C, 36.08; H, 1.51; N, 8.42; S,38.53; Cl, 10.65. Found: C, 36.26; H, 1.45; N, 8.68; S, 38.71, Cl,10.73.

EXAMPLE 40 3-[(1,3-Benzodithiol-2-ylidene)amino]-5-(phenylmethylene)-2-thioxo-4-thiazolidinone

A mixture of 2.0g of 3-[(1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone (see example 37), benzaldehyde (20 ml, excess)and pyridinium acetate (5 ml) is prepared and heated at 120° C for 3days under nitrogen with stirring. The mixture is then cooled, dilutedwith ether and filtered. The residue is washed with water andrecrystallized from dimethylformamide to yield 2.2 g of the titlecompound, melting point 288°-289° C.

Anal. Calc'd. for C₁₇ H₁₀ N₂ OS₄ : C, 52.82; H, 2.61; N, 7.25; S, 33.18.Found: C, 53.02; H, 2.74; N, 7.07; S, 33.04.

EXAMPLE 413-[(1,3-Benzodithiol-2-ylidene)amino]-5-pentylidene-2-thioxo-4-thiazolidinone

A slurry of 2.0g of 3-[(1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone (see example 37), valeraldehyde (10 ml,excess) and acetic acid/piperidine (2:1) (10 drops) in anhydrous slyme(400 ml) is heated at reflux for eighteen hours. The reaction mixture ischilled in an ice bath and the resultant precipitate collected byfiltration. This precipitate (1.6 g) is recrystallized from 50 ml ofdimethylformamide to yield 1.1 g of the title compound, melting point210°-212° C.

Anal. Calc'd. for C₁₅ H₁₄ N₂ OS₄ : C, 49.15; H, 3.85; N, 7.64; S, 34.99.Found: C, 49.32; H, 3.74; N, 7.39; S, 34.73.

EXAMPLE 423-[(1,3-Benzodithiol-2ylidene)amino]-5-tetradecyclidene-2-thioxo-4-thiazolidinone

A slurry of 2.0g of 3-[(1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone (see example 37), tetradecyl aldehyde (20 g,excess) and acetic acid/piperidine (10 drops) in anhydrous glyme (400ml) is heated at reflux for eighteen hours. The reaction mixture iscooled in an ice bath and the resultant precipitate collected byfiltration. This precipitate is recrystallized from 75 ml ofdimethylformamide to yield 2 g of the title compound, melting point180°-181° C.

Anal. Calc'd. for D₂₄ H₃₂ N₂ OS₄ : C, 58.50; H, 6.55; N, 5.68; S, 26.02.Found: C, 58.62; H, 6.42; N, 5.48; S, 26.28.

EXAMPLE 435-[3-[(1,3-Benzodithiol-2-ylidene)amino]-4-oxo-2-thioxo-5thiazolylidene]pentanoicacid, methyl ester

A slurry of 2.98g of 3-[(1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone (see example 37), methyl-5-pentanaloate (10g, excess) and acetic acid/piperidine (10 drops) in 400 ml of anhydrousglyme is heated at reflux for eighteen hours. The reaction mixture ischilled in an ice bath and the resultant precipitate collected byfiltration. The yellow product is recrystallized from dimethylformamideto yield 2.3g of the title compound, melting point 210° C.

Anal. Calc'd. for C₁₆ H₁₄ N₂ O₃ S₄ : C, 46.81; H, 3.44; N, 6.82; S,31.24. Found: C, 46.91; H, 3.29; N, 6.99; S, 31.28.

EXAMPLE 44 3-[(1,3-Benzodithiol-2-ylidene)amino]-5-octylidene-2-thioxo-4-thiazolidinone

A slurry of 2.0g of 3-[(1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone (see example 37), octanal (15 ml, excess) andacetic acid/piperidine (10 drops) in anhydrous glyme (400 ml) is heatedat reflux for 18 hours. The reaction mixture is chilled in an ice bathand the resultant precipitate collected by filtration. The precipitateis recrystallized twice from dimethylformamide to yield 1.02g of thetitle compound, melting point 185° C.

Anal. Calc'd. for C₁₈ H₂₀ N₂ OS₄ : C, 52.91; H, 4.93; N, 6.86; S, 31.38Found: C, 52.97; H, 4.78; N, 6.92; S, 31.27

EXAMPLE 45 3-(1,3-Benzodithiol-2-ylideneamino)-5-(2-phenylethylidene)-2-thioxo-4-thiazolidinone

A slurry of 2.98g of 3-[(1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone (see example 37), phenylacetaldehyde (10 ml,excess) and acetic acid/piperidine (10 drops) in 600 ml of anhydrousglyme is heated at reflux for 4 days. The reaction mixture is filteredwhile hot, and the solid is collected and recrystallized fromdimethylformamide to yield 1.78 g of the title compound, melting point233°-234° C.

Anal. Calc'd. for C₁₈ H₁₂ N₂ OS₄ : C, 53.98; H, 3.02; N, 6.99; S, 32.02.Found: C, 54.05; H, 2.90; N, 7.23; S, 31.84.

EXAMPLE 46 3-[(1,3-Benzodithiol-2-ylidene)amino]-2-thioxo-5-[[3-(trifluoromethyl)phenyl]methylene]-4-thiazolidinone

A slurry of 3-[(1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone (see example 37), m-trifluoromethylbenzaldehyde(10 ml, excess) and acetic acid/piperidine (1 ml) in 250 ml of anhydrousglyme is heated at reflux for seven days. The reaction mixture isconcentrated in vacuo and the oily residue extracted with hexane. Thesolid thus obtained is slurried in 1000 ml of dichloromethane andstirred at room temperature overnight. The slurry is filtered and thefiltrate concentrated in vacuo. The solid residue thus obtained isrecrystallized from dimethylformamide to yield 500 mg of the titlecompound, melting point 268°-269° C.

Anal. Calc'd. for C₁₈ H₉ N₂ S₄ F₃ O: C, 47.57; H, 2.00; N, 6.16; S,28.21; F, 12.54. Found: C, 47.83; H, 1.91; N, 6.36; S, 28.43; F, 12.78.

EXAMPLE 47 3-[(5-Methoxy-1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone

A slurry of 4.15g of N-(5-methoxy-1,3-benzodithiol-2-ylidene)-N-methylbenzaminium iodide, N-aminorhodanine (1.48 g, 0.01mole) and sodium carbonate (530 mg, 0.005 mole) in 100 ml ofdimethylformamide is heated at 120° C for 2 hours. The reaction mixtureis chilled in an ice bath and the resultant precipitate collected byfiltration. The product is recrystallized from dimethylformamide toyield 2.23 g of the title compound, melting point 254°-255° C.

Anal. Calc'd. for C₁₁ H₈ N₂ O₂ S₄ : C, 40.23; H, 2.46; N, 8.53; S,39.05. Found: C, 40.27; H, 2.37; N, 8.70; S, 38.83.

EXAMPLE 482-Thioxo-3-[[5-(trifluoromethyl)-1,3-benzodithiol-2-ylidene]amino]-4-thiazolidinone

A slurry of 3.0g of N-methyl-N-[5-(trifluoromethyl)-1,3-benzodithiol-2-ylidene]benzaminium iodide, N-aminorhodanine (982 mg)and sodium carbonate (351 mg) in 100 ml of anhydrous dimethylformamideis heated at 120° C for 2 hours. The reaction mixture is chilled in anice bath and the resultant precipitate collected by filtration. Thisproduct is recrystallized from dimethylformamide to yield 570 mg of thetitle compound, melting point 285°-288° C.

Anal. Calc'd. for C₁₁ H₅ F₃ N₂ OS₄ : C, 36.06; H, 1.38; N, 7.65; S,35.00; F, 15.56. Found: C, 36.14; H, 1.26; N, 7.89; S, 35.16; F, 15.61.

EXAMPLE 493-[(5-Nitro-1,3-benzodithiol-2-ylidene)amino]-2-thioxo-4-thiazolidinone

A slurry of 4.24g of N-methyl-N-(5-nitro-1,3-benzodithiol-2-ylidene)benzaminium iodide, N-aminorhodanine (1.47 g), and sodiumcarbonate (523 mg) in 100 ml of dimethylformamide is heated at 120°-140°for two hours. The reaction solution is chilled in an ice water bath andthe resultant precipitate collected by filtration. The precipitate isrecrystallized twice from dimethylformamide to yield 1.2 g of the titlecompound, melting point 315° C.

Anal. Calc'd. for C₁₀ H₅ N₃ O₃ S₄ : C, 34.98; H, 1.47; N, 12.24; S,37.34. Found: C, 35.20; H, 1.36; N, 12.49; S, 37.62.

EXAMPLES 50-52

Following the procedure of example 25, but substituting the compoundlisted in column I for N-(aminoethyl)morpholine and the compound listedin column II for N-(1,3-benzodithiol-2-ylidene)-N-methylbenzaminiumiodide, yields the compound listed in column III.

    __________________________________________________________________________           Column I        Column II     Column III                               __________________________________________________________________________    N-(aminopropyl)thiamorpholine                                                                 5-methyl-N-methyl-N-N-phenyl-                                                               N-(5-methyl-1,3-benzodithiol-                                   1,3-benzodithiol-2-iminium                                                                  2-ylidene)-4-thiamorpholine-                                    iodide        propaneamine                                    N-(aminoethyl)piperazine                                                                      5-hydroxy-N-methyl-N-phenyl-                                                                N-(5-hydroxy-1,3-benzodithiol-                                  1,3-benzodithiol-2-iminium                                                                  2-ylidene)-1-piperazine-                                        iodide        ethaneamine                                     N-(aminoethyl)pyrrolidine                                                                     5-bromo-N-methyl-N-phenyl-                                                                  N-(5-bromo-1,3-benzodithiol-                                    1,3-benzodithiol-2-iminium                                                                  2-ylidene)-1-pyrrolidine-                                       iodide        ethaneamine                                     __________________________________________________________________________

What is claimed is:
 1. A compound having the formula ##STR14## or apharmaceutically acceptable salt thereof, wherein R₁ is hydrogen,halogen, trifluoromethyl, alkyl, alkoxy, nitro, amino or hydroxy; R₁₂ ishydrogen or alkyl; and n is 0, 1, 2, 3, 4 or 5; wherein the terms"alkyl" and "alkoxy" refer to groups having 1 to 4 carbon atoms.
 2. Acompound in accordance with claim 1 wherein R₁ is hydrogen.
 3. Acompound in accordance with claim 1 wherein R₁ is halogen.
 4. A compoundin accordance with claim 1 wherein n is
 0. 5. A compound in accordancewith claim 1 wherein n is 1, 2, 3, 4 or
 5. 6. A compound in accordancewith claim 1 wherein R₁₂ is hydrogen.
 7. A compound in accordance withclaim 1 wherein R₁₂ is alkyl.
 8. The compound in accordance with claim 1having the name [(1,3-benzodithiol-2-ylidene)amino]acetic acid, ethylester.
 9. The compound in accordance with claim 1 having the name3-[(1,3-benzodithiol-2-ylidene)amino]propanoic acid, ethyl ester. 10.The compound in accordance with claim 1 having the name[(1,3-benzodithiol)-2-ylidene)amino]acetic acid.
 11. The compound inaccordance with claim 1 having the name3-[(1,3-benzodithiol-2-ylidene)amino]propanoic acid.
 12. The compound inaccordance with claim 1 having the name4-[(1,3-benzodithiol-2-ylidene)amino]butanoic acid, ethyl ester.
 13. Thecompound in accordance with claim 1 having the name[(1,3-benzodithiol-2-ylidene)amino]butanoic acid.
 14. The compound inaccordance with claim 1 having the name3-[(1,3-benzodithiol-2-ylidene)amino]propanoic acid, methyl ester. 15.The compound in accordance with claim 1 having the name3-[(1,3-benzodithiol-2-ylidene)amino]propanoic acid, 1-methylethylester.
 16. The compound in accordance with claim 1 having the name3-[(1,3-benzodithiol-2-ylidene)amino]propanoic acid, butyl ester. 17.The compound in accordance with claim 1 having the name3-[(5-chloro-1,3-benzodithiol-2-ylidene)amino]butanoic acid, ethylester.
 18. The compound in accordance with claim 1 having the name3-[(1,3-benzodithiol-2-ylidene)amino]butanoic acid, methyl ester. 19.The compound in accordance with claim 1 having the name3-[(1,3-benzodithiol-2-ylidene)amino]butanoic acid, 1-methylethyl ester.20. The compound in accordance with claim 1 having the name3-[(1,3-benzodithiol-2-ylidene)amino]butanoic acid, butyl ester.
 21. Thecompound in accordance with claim 1 having the name3-[(5-chloro-1,3-benzodithiol-2-ylidene)amino]propanoic acid, ethylester.